Clinical lung transplantation is now an accepted treatment modality for many adults with end-stage pulmonary diseases. Recently, this technique has been extended to the pediatric age group. For infants and children, two lung transplant options exist: 1) size matched immature cadaveric whole lungs, or 2) lobes or segments of already mature lungs (reduced size transplant). The use of mature adult lobes for transplantation would greatly increase the donor pool for the pediatric population. Several questions concerning pediatric pulmonary transplantation remain extant: 1) what type of transplant will provide superior long term function for the pediatric recipient - an immature whole lung or a reduced-size mature lobar transplant?, 2) what are the long term effects of transplantation on the development, growth, and function of an immature whole lung?, 3) what are the effects of transplantation on the ability of the immature lung to respond to challenge (hypoxia, increased pulmonary blood flow)?, and 4) what are the effects of transplantation on the airway mechanics and vascular resistance of a mature lobe functioning as a lung. This study proposes to examine the effects of reimplantation alone versus transplantation with its associated immunosuppression and chronic rejection on the growth, development, pulmonary airway and vascular function in a pig model of pediatric lung transplantation. Growth and development will be assessed using standard morphometric methods in an effort to distinguish true growth from hyperexpansion: changes in lung volume, changes in wet weight with correlated extravascular lung water, changes in terminal airway and alveolar dimensions, and changes in total alveolar number. Pulmonary airway and vascular function measurements will be made both in the resting and challenged (hypoxia, increased blood flow) states. Measurements will be made in innervated lungs of immature and mature adult animals to establish baseline values. Immature piglets will have either 1) reimplantation of an autologous immature lung, 2) transplantation of an allograft immature lung, or 3) transplantation of a mature lobe. After recovery for 14 weeks, with appropriate immunosuppression when indicated, measurements of growth and function will be made and compared to the obtained baseline values and to each other with appropriate statistical methods. These studies will afford insight and understanding into the effects of pulmonary transplantation on subsequent growth and function of lung transplants in the pediatric recipient.
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